The mechanisms initiating human labor remain poorly understood, severely limiting modern clinical medicine's efforts to resolve the problems of pre- and post-term delivery. Sadly, the consequences of such untimely labor and delivery can devastate the expectant parents, both emotionally and financially. The infant's prematurity-induced debility, can incur enormous costs to society, and posing one of the most wrenching moral dilemmas of our time. For these reasons, research clarifying the mechanisms of labor is imperative. Most mediators governing labor are produced or act juxta-placentally, i.e., in the local environment of the placenta, and endometrium (decidua). I propose to investigate the local regulation of myometrial activity by monitoring locally mediated events in the actual environment where they induce myometrical activity. I will develop four techniques for juxta-placental study in pregnant sheep: a) dialysis of the interendometriochorial space (IECS); b) local lymphatic sampling; c) local vascular infusion of regulators of myometrical activity involved in the onset of labor; and d) measurement of tissue concentrations of regulatory substances from this site. In years 4 and 5, I will conduct parallel work in the nonhuman primate to address questions specifically concerning human parturition.